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Increased blood vessel receptor protein expression found in female mice may explain differences in MS incidence rates between women and men

May 15, 2014

Background:

MS is a disease with a strong sex bias, with women being up to
four times more likely to be affected than men. The reasons for
this difference remain unclear; however, researchers have
indicated genetic, hormonal and environmental contributions.
A study that was
recently conducted at the Washington University School of
Medicine in St. Louis, Missouri may be able to provide more
insight into this issue and future therapeutic strategies.

The Study:

Dr. Lillian Cruz-Orengo and colleagues looked at a strain of mice
that exhibits MS-like characteristics in order to investigate the
sex difference in MS incidence. By examining DNA segments from
female and male mice, they were able to investigate levels of
proteins in the central nervous system (CNS), composed of the
brain and spinal cord, to determine if there are any significant
differences between genders. The team also looked at postmortem
human CNS tissue from 20 subjects, of which 10 had MS and 10 did
not.

Results:

DNA analysis revealed differences in activation of up to 20 genes
in the CNS of female mice versus male mice. One of the genes,
which codes for a blood vessel protein called S1PR2, was found at
higher levels in female mice. This increase was also found in
areas of the CNS that are more susceptible to MS. The follow-up
with the postmortem brain tissue supported the findings in mice,
with the highest levels of S1PR2 being found in two females with
relapse-remitting MS. The researchers discovered that S1PR2 has
an important role because it regulates which cells can travel
through the blood-brain barrier (BBB). By treating the mice with
an agent that blocks S1PR2, researchers were able to lessen the
MS disease.

Comment:

This is the first study which identifies sexual differences in
structures of the brain which may explain why females are more
vulnerable to developing MS than males. Researchers suggest that
increased levels of S1PR2 in disease-susceptible regions of the
CNS of females may lead to increased numbers of immune cells
entering the CNS and causing inflammation.

In addition to providing clues about gender differences in MS
incidence, results from this study offer implications for the
development of treatments for relapsing-remitting MS. Drugs that
target S1PR2, specifically by decreasing its activity or
expression, may help to limit the entry of cells that lead to
inflammation of the CNS. Currently there is a MS drug called
Gilenya
that is available to the public and targets other proteins that
are in the same family as S1PR2. Further research will be
required in order to validate these study findings and lead to
the development of a drug that can target S1PR2.